Pharmaceutical compositions and methods for the prevention and treatment of hearing loss

Abstract

This invention relates to soba tertide (N succinyl-[Glu 9 ,Ala 11,15 This invention relates to a composition for promoting the proliferation and protection of existing neuroepithelium of cochlear and vestibular cells located within the otolaryngeal vesicle using endothelin B receptor agonists such as endothelin 1 (IRL-1620). The composition is administered systemically via transtympanic membrane, cochlear fenestration, or intravenously or intramuscularly. This invention also relates to a method for treating sensorineural hearing loss and vestibular symptoms caused by inner ear cell degeneration by using compounds containing endothelin analogs, through mechanisms of neuroprotection and neurogenesis of cochlear vestibular hair cells and synapses.

Claims

1. N-succinyl-[Glu ９ , Ala １１，１５ Endothelin 1 (IRL-1620) (Soba terutide), BQ-3020, [Ala １，３，１１，１５ ] - Endothelin, Sa Selected from the group consisting of lafotoxin S6c, endothelin-3, and mixtures thereof. A pharmaceutical composition comprising an endothelin B receptor analog.

2. The solvent for administering endothelin B receptor analogs is Gelfoam®. Hyaluronic acid gel, Seprapack (trademark), thiol-modified hyaluronic acid, porcine-type hyaluronic acid Lagen glutaraldehyde crosslinked product, gelatin, chitosan sugar chain derivative, Poloxam via sustained-release drug delivery systems such as ER 407 and chitosan glycerophosphate hydrogel. The sustained release consists of lipid core nanocapsules and poly-L-lysine (HBPL) nanoparticles. The pharmaceutical composition described in item 1.

3. The dosage range for the endothelin analog is 0.00001 to approximately 1 mg, according to claim 1. The pharmaceutical composition described.

4. Using compounds containing endothelin analogs, cochlear vestibular hair cells, supporting cells and cina The neuroprotective and neurogenesis mechanisms of Puss are caused by the degeneration of inner ear cells. Methods for treating sensorineural hearing loss and vestibular symptoms.

5. The aforementioned cochlear vestibular hair cells, supporting cells, and synapses are spiral ganglion neurons and / or The method according to claim 4, wherein the cells are inner hair cells and / or outer hair cells.

6. Additional agents such as growth factors, osmotic agents such as glycerol, and furosemide or ethacrine acid. Diuretics, or steroids, or transplanted stem cells, or ferulic acid, or arctigenin n, or Espin isoform 1 polypeptide, or glial cell line-derived neurotrophic compounds Child, brain-derived neurotrophic factor, neurotrophic factor-3, neurotrophic factor-4 / 5, and ciliated neurotrophic factor A neurotrophic factor selected from a group consisting of nutrient factors, or human insulin-like growth factor 1, Trin 1 or mixtures thereof, and can optionally be used together with excipients, etc. The method according to claim 4, comprising the pharmaceutical composition described in claim 1.

7. Endothelin B receptor analogs cross the middle ear barrier to enter the cochlear vestibular system. It is delivered intratympanically by a diffusion-based treatment, and the treatment is performed using Silverstein Microw This may be an intratympanic injection using a cymbal, round window microcatheter, or hollow needle, claim The method described in item 4.

8. Endothelin B receptor analogs are administered via cochlear fenestration, direct injection, osmotic minipump, and The method according to claim 4, wherein the drug is delivered into the cochlea by a procedure via a reciprocating perfusion system.

9. Endothelin B receptor analogs stimulate the vestibule through treatment via the endolymphatic sac and endolymphatic vessels. The method according to claim 4, which is delivered internally.

10. Endothelin B receptor analogs are delivered intravenously, orally, intramuscularly, or subcutaneously, claim. The method described in 4.

11. Endothelin B receptor analogs are coated onto cochlear implantable devices. The method according to claim 4, which is delivered intracavitarially.

12. Endothelin B receptor analogs are nanoparticles containing stealth nanoparticles and hydrogels. The method according to claim 4, wherein the child is combined with the child.

13. The pharmaceutical composition according to claim 1 is effective in treating balance disorders, ear fullness, tinnitus, and variable sensorineural hearing loss. Sudden sensorineural hearing loss, noise-induced hearing loss, vestibular neuritis, Meniere's disease, labyrinthitis, drug-induced sensorineural hearing loss It is used to treat hearing loss, sensorineural hearing loss due to genetic disorders, congenital sensorineural hearing loss, and auditory nerve disorders. method.

14. Endothelin analog administration involves additional agents such as growth factors, osmotic agents such as glycerol, and Diuretics such as rosemide or ethacrine, or steroids, or transplanted stem cells, Ferulic acid, or arctigenin, or Espin isoform 1 polypeptide, or glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, neurotrophic factor-3, neurotrophic A neurotrophic factor selected from the group consisting of Factor-4 / 5 and ciliary neurotrophic factors, or It can be combined with human insulin-like growth factor 1, netrin 1, or a mixture thereof. The method according to claim 4, which can be combined or used with.

15. (a) Endothelin B (ET) Ｂ ) Receptor agonists and steroids or their salts A packaging composition comprising, (b) The ET for treating the patient Ｂ Receptor agonists and the steroid or Package inserts for simultaneous or sequential administration of those salts, (c) Containers for (a) and (b), A manufactured article that is equipped with the following features.

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